Abstract: Syndrome differentiation and mechanism observation are the keys to the traditional Chinese medicine (TCM) clinical practice. They are also crucial to the improvement of clinical efficacy. This study gives a detailed explanation of the speculation system of syndrome differentiation and mechanism observation: speculating according to the chronological order of occurrence and development of diseases and syndromes (vertical speculation), along with speculating on the elements of syndromes and mechanism in an appositive way (horizontal speculation). In addition, the differentiation and analysis of the various influencing factors of syndromes and diseases are supplements to the combination of the vertical and horizontal speculations. The collection and analysis of the four diagnostic information form the basis of that combination speculations. Besides, we propose the dynamically integrated relationship of speculation on the complex mechanism and the speculation model of syndrome differentiation and mechanism observation by incorporating modern scientific methods. Thus, it has a certain guidance value for the research of the theory of syndrome differentiation and mechanism in TCM.